Objective To assess the causal relationship between coffee intake and prostate cancer risk by using the two-sample Mendel randomization (MR) method. Methods The genome-wide association study (GWAS) data on coffee intake (exposure) and prostate cancer (outcome) were obtained from two independent data sets in UK Biobank. The inverse variance weighted method (IVW), weighted median estimator method (WME), and MR-Egger method were used for MR analyses. The OR value and 95%CI were used to represent the association between coffee intake and prostate cancer. In addition, the MR-Egger method was performed for pleiotropic and heterogeneity tests, and the leave-one-out method was used for sensitivity analysis. Results A total of 38 SNP were selected as instrumental variables. The IVW method showed that coffee intake might reduce the risk of prostate cancer (OR=0.994; 95%CI: 0.990-0.999; P=0.009). The WME method obtained the same conclusions (OR=0.991; 95%CI: 0.985-0.999; P=0.018), but MR-Egger regression did not find a causal relationship between coffee intake and prostate cancer (OR=0.992; 95%CI: 0.983-1.000; P=0.084). The MR-Egger method showed no pleiotropy (intercept=4.2E-5; P=0.581) or heterogeneity (Q=27.20; P=0.854) among the instrumental variables. The sensitivity analysis indicated that the conclusion was robust. Conclusion Two-sample Mendel randomization analysis reveals that coffee consumption might reduce the risk of prostate cancer.

Objective To investigate the effect of microRNA-223(miR-223)on prostate cancer cell damage by regulating the Kelch-like epichlorohydrin related protein 1(Keap1)/nuclear factor E2 related factor 2(Nrf2)/antioxidant response element(ARE)signaling pathway.Methods The prostate cancer cell line PC3 was cultured and randomly divided into control,down-regulated miR-223,and up-regulated miR-223 groups.Changes in miR-223 expression,cell proliferation rate,cell migration number,cell invasion number,apoptosis rate,and expression level of Keap1/Nrf2/ARE signaling pathway were explored.Results Compared with the control group,the cell invasion number,cell migration number,cell proliferation rate,Nrf2 and ARE expression increased at 24,48 and 72 h in down-regulated miR-223 group,while the expressions of miR-223,Keap1 and apoptosis rate decreased(P<0.05).Compared with the down-regulated miR-223 group,24,48 and 72 h cell proliferation rate,cell invasion number,cell migration number,ARE and Nrf2 expression decreased in the up-regulated miR-223 group,while miR-223,apoptosis rate and Keap1 expression increased(P<0.05).Conclusion Regulation of miR-223 effectively ameliorates prostate cell injury,and the mechanism may be related to the Keap1/Nrf2/ARE signaling pathway.